Azelastine is a phthalazinone derivative having the following structural formula ##STR1##
The chemical designation of azelastine is: 4-(4-chlorobenzyl)-2-(perhydro-1 methylazepine-4-yl)-1-(2H) phthalazinone. Azelastine is particularly useful in asthma prophylaxis. Azelastine also has anti-allergic and antihistaminic properties, see German Patent No. 21 64 058.
Azelastine dissolves to the extent of 0.005 % in water at 20.degree. C.
Previously used salts of azelastine display the following solubility in water at 20.degree. C.:
hydrochloride: 1% PA1 embonate: 0.0015% PA1 succinate PA1 phosphate: solubility PA1 maleate: in water at 20.degree. C. PA1 citrate: ca. 1% PA1 methane sulphonate PA1 fumarate PA1 toluene sulphonate: under 1% PA1 benzene sulphonate PA1 tartrate PA1 acetate: more than 10% PA1 gluconate: up to 55% PA1 lactate: more than 10% PA1 malate: 3% PA1 azelastine gluconate: 0.1-50, preferably 1-50 percent by weight PA1 azelastine acetate: 0.1-20, preferably 1-20 percent by weight PA1 azelastine lactate: 0.1-20, preferably 1-20 percent by weight PA1 azelastine malate: 0.1-5, preferably 1-3 percent by weight
Other salts of azelastine have the following solubilities:
The solubilities quoted, as well as the marked dependence of solubility on temperature, result in the salts not being suitable for the preparation of pharmaceutical formulations having a higher content of dissolved azelastine. The preparation of locally applied formulations, in particular those with a limited water content (for example emulsion ointments and creams as well as gels) call for the availability of more highly concentrated aqueous solutions in order to provide the required amounts of active substances to the skin or mucous membrane.